Acquisition of complement fixing antibodies targeting Plasmodium falciparum merozoites in infants and their mothers in Uganda.
Antibody-mediated complement fixation has previously been associated with protection against malaria in naturally acquired immunity. However, the process of early-life development of complement-fixing antibodies in infants, both in comparison to their respective mothers and to other immune parameters, remains less clear. We measured complement-fixing antibodies in newborns and their mothers in a malaria endemic area over 5 years follow-up and found that infants' complement-fixing antibody levels were highest at birth, decreased until six months, then increased progressively until they were similar to birth at five years. Infants with high levels at birth experienced a faster decay of complement-fixing antibodies but showed similar levels to the low response group of newborns thereafter. No difference was observed in antibody levels between infant cord blood and mothers at delivery. The same result was found when categorized into high and low response groups, indicating placental transfer of antibodies. Complement-fixing antibodies were positively correlated with total schizont-specific IgG and IgM levels in mothers and infants at several time points. At nine months, complement-fixing antibodies were negatively correlated with total B cell frequency and osteopontin concentrations in the infants, while positively correlated with atypical memory B cells and P. falciparum-positive atypical memory B cells. This study indicates that complement-fixing antibodies against P. falciparum merozoites are produced in the mothers and placentally-transferred, and they are acquired in infants over time during the first years of life. Understanding early life immune responses is crucial for developing a functional, long lasting malaria vaccine.


Kinematics and spatiotemporal parameters of infant-carrying in olive baboons.
In the field of biomechanics of quadrupedal locomotion in primates, infant-carrying has received little attention. This study presents the first biomechanical study of infant-carrying in captive female olive baboons (Papio anubis). We test whether females carrying infants conform 1) to the Support Polygon Model (Rollinson and Martin: Symp Zool Soc Lond 48 (1981) 377-427) of gait selection, according to which diagonality should decrease when the infant is carried cranially and increase when the infant is carried dorsally and caudally; 2) to Biewener's (Biewener: Science 245 () 45-48) theory of limb postures, according to which females should extend their hind limbs more due to infant load, especially in the later stages when the infant is not fully autonomous but relatively heavy. This study focuses on the sagittal kinematics of quadrupedal gaits (joint angles and spatiotemporal parameters) of four females with and without infant loads at the CNRS Primatology Station (France). High-speed video recordings were made using the technical platform "Motion Analysis of Primates" available in the animals' place of life. Regarding diagonality, our results do not fully conform to those predicted by the Support Polygon Model of gait selection; however, the model cannot be rejected at this stage in experiment. With regard to limb posture, our results do not support Biewener's (Biewener: Science 245 () 45-48) theory: loaded females do not extend their hind limbs more as predicted; on the contrary, the hind limbs tend to be more flexed when the infant they carry is relatively heavy.


Elimination of a hydroxyl group in FTY720 dramatically improves the phosphorylation rate.
The new immunosuppressant FTY720 (fingolimod), an analog of the endogenous lipid sphingosine, induces transient lymphopenia through the sequestration of lymphocytes in secondary lymphoid organs. Phosphorylation of FTY720 by sphingosine kinase 2 (SphK2) yields the active metabolite FTY720-phosphate (FTY-P), which induces lymphopenia through agonism of the sphingosine 1-phosphate receptor S1P(1) on endothelial cells and lymphocytes. Dephosphorylation of circulating FTY-P creates an equilibrium between FTY720 and its phosphate, and results with human patients indicate that phosphorylation of FTY720 could be rate limiting for efficacy. We report that the FTY720 derivative 2-amino-4-(4-heptyloxyphenyl)-2-methylbutanol [AAL(R)] is phosphorylated much more rapidly than FTY720 in cultured human cells and whole blood. The K(cat) for AAL(R) with recombinant SphK2 is 8-fold higher than for FTY720, whereas the K(m) for the two substrates is very similar, indicating that the increased rate of phosphorylation results from faster turnover by SphK2 rather than a higher binding affinity. Consequently, treating cells with AAL(R), but not FTY720, triggers an apoptotic pathway that is dependent on excessive intracellular accumulation of long-chain base phosphates. In agreement with the in vitro results, phosphorylation of AAL(R) is more complete than that of FTY720 in vivo (mice), and AAL(R) is a more potent inducer of lymphopenia. These differences may be magnified in humans, because phosphorylation of FTY720 is much less efficient in humans compared with rodents. Our results suggest that AAL(R) is a better tool than FTY720 for in vivo studies with S1P analogs and would probably be a more effective immunosuppressant than FTY720.


Are Americans receptive to smokefree bars?
It is not known whether the American public accepts smokefree bars and restaurants. Anticipating public displeasure with these ordinances, tobacco, liquor and restaurant industry trade associations have helped to stall efforts to pass laws curbing bar and restaurant smoking in the expectation that diminished patronage would inevitably result. This cross-sectional trend study uses data from the May 1993 and January 1999 Current Population Surveys, Tobacco Use Supplements to compare tobacco-control attitudes among American bar and restaurant workers, all other workers, smokers and nonsmokers (total n = 90,661). It was found that by 1999, smokefree workplaces were widely accepted by two-thirds of adults, with half favoring completely smokefree restaurants. Completely smokefree bars remained less popular, with nearly equal numbers (about 30%) preferring them or favoring unrestricted bar smoking. Even among bar and restaurant industry workers less than 10% favored unrestricted restaurant smoking. Greater acceptances of smokefree bars are now taking hold, especially in places like California, where acceptance rose 15% in six years, and 45% preferred them. Opponents to smokefree bars and restaurants may have underestimated the levels of support and growing acceptance of smokefree living areas now taking hold among the general public.


Chest physiotherapy for patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease (COPD): a systematic review.
To examine the effectiveness of chest physiotherapy for patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease (COPD). CINAHL, MEDLINE, Embase, Cochrane, Expanded Academic Index, Clinical Evidence, PEDro, Pubmed, Web of Knowledge and Proquest were searched from the earliest available time to September 2007, using the key elements of COPD, acute exacerbation and chest physiotherapy interventions. To be included, trials had to investigate patients during admission to hospital with an acute exacerbation of COPD, and to evaluate at least one physiotherapy intervention. Two reviewers independently applied the inclusion criteria, and assessed trial quality using the PEDro scale. Results were expressed as standardised mean differences and analysed qualitatively with a best-evidence synthesis. Thirteen trials were identified. There was moderate evidence that intermittent positive pressure ventilation and positive expiratory pressure were effective in improving sputum expectoration. In addition, there was moderate evidence that walking programmes led to benefits in arterial blood gases, lung function, dyspnoea and quality of life. No evidence was found supporting the use of any other chest physiotherapy techniques to change lung function, arterial blood gases, perceived level of dyspnoea or quality of life. Chest physiotherapy techniques such as intermittent positive pressure ventilation and positive expiratory pressure may benefit patients with COPD requiring assistance with sputum clearance, while walking programmes may have wider benefits for patients admitted with an exacerbation of COPD. Chest physiotherapy techniques other than percussion are safe for administration to this patient population.


A computer-aided diagnosis system of nuclear cataract.
Cataracts are the leading cause of blindness worldwide, and nuclear cataract is the most common form of cataract. An algorithm for automatic diagnosis of nuclear cataract is investigated in this paper. Nuclear cataract is graded according to the severity of opacity using slit lamp lens images. Anatomical structure in the lens image is detected using a modified active shape model. On the basis of the anatomical landmark, local features are extracted according to clinical grading protocol. Support vector machine regression is employed for grade prediction. This is the first time that the nucleus region can be detected automatically in slit lamp images. The system is validated using clinical images and clinical ground truth on >5000 images. The success rate of structure detection is 95% and the average grading difference is 0.36 on a 5.0 scale. The automatic diagnosis system can improve the grading objectivity and potentially be used in clinics and population studies to save the workload of ophthalmologists.


Role of iodine oxoacids in atmospheric aerosol nucleation.
Iodic acid (HIO3) is known to form aerosol particles in coastal marine regions, but predicted nucleation and growth rates are lacking. Using the CERN CLOUD (Cosmics Leaving Outdoor Droplets) chamber, we find that the nucleation rates of HIO3 particles are rapid, even exceeding sulfuric acid-ammonia rates under similar conditions. We also find that ion-induced nucleation involves IO3 - and the sequential addition of HIO3 and that it proceeds at the kinetic limit below +10°C. In contrast, neutral nucleation involves the repeated sequential addition of iodous acid (HIO2) followed by HIO3, showing that HIO2 plays a key stabilizing role. Freshly formed particles are composed almost entirely of HIO3, which drives rapid particle growth at the kinetic limit. Our measurements indicate that iodine oxoacid particle formation can compete with sulfuric acid in pristine regions of the atmosphere.


ET-MSF: a model stacking framework to identify electron transport proteins.
The electron transport chain is closely related to cellular respiration and has been implicated in various human diseases. However, the traditional "wet" experimental method is time consuming. Therefore, it is key to identify electron transport proteins by computational methods. Many approaches have been proposed, but performance of them still has room for further improvement. Methodological issues: In our study, we propose a model stacking framework, which combines multiple base models. The protein features are extracted via PsePSSM from protein sequences. Features are fed into the base model including support vector machines (SVM), random forest (RF), XGBoost, etc. The results of base model are entered into logistic regression model for final process. On the independent dataset, the accuracy and Matthew's correlation coefficient (MCC) of proposed method are 95.70% and 0.8756, respectively. Furthermore, we show that the model stacking framework outperforms single machine learning classifiers statistically. Our models are better than most known strategies for identifying electron transport proteins. Our model can be used to more precisely identify electron transport proteins.


As others see us.
If it is to be fully effective, functional activity in business needs to see itself as an integral part of management and not as some specialist, separate adjunct. The so-called professions often find this difficult to contemplate, let alone achieve. In Unilever's UK operations, occupational health activity and staff are effectively integrated into general management and, as a direct consequence, the business benefits and the participants reach higher levels of job satisfaction.


Stabilization of microtubule dynamics by estramustine by binding to a novel site in tubulin: a possible mechanistic basis for its antitumor action.
The cellular targets for estramustine, an antitumor drug used in the treatment of hormone-refractory prostate cancer, are believed to be the spindle microtubules responsible for chromosome separation at mitosis. Estramustine only weakly inhibits polymerization of purified tubulin into microtubules by binding to tubulin (Kd, approximately 30 microM) at a site distinct from the colchicine or the vinblastine binding sites. However, by video microscopy, we find that estramustine strongly stabilizes growing and shortening dynamics at plus ends of bovine brain microtubules devoid of microtubule-associated proteins at concentrations substantially below those required to inhibit polymerization of the microtubules. Estramustine strongly reduced the rate and extent both of shortening and growing, increased the percentage of time the microtubules spent in an attenuated state, neither growing nor shortening detectably, and reduced the overall dynamicity of the microtubules. Significantly, the combined suppressive effects of vinblastine and estramustine on the rate and extent of shortening and dynamicity were additive. Thus, like the antimitotic mechanisms of action of the antitumor drugs vinblastine and taxol, the antimitotic mechanism of action of estramustine may be due to kinetic stabilization of spindle microtubule dynamics. The results may explain the mechanistic basis for the benefit derived from combined use of estramustine with vinblastine or taxol, two other drugs that target microtubules, in the treatment of hormone-refractory prostate cancer.


Determination of atmospheric structure function by using a single coherent detector.
The wave structure function associated with atmospheric turbulence is important in the effective design of telescopes for coherent optical receivers. This paper describes a method of measurement of the wave structure function by employing an already existing optical receiver. The aperture of this receiver's telescope is masked by an opaque screen with two small holes. It is then shown that when the incident beam obeys Gaussian statistics, the receiver's A.M. output can be simply related to the wave structure function of the incident beam.


Psychological test performance during experimental challenge to toluene and n-butyl acetate in cases of solvent-induced toxic encephalopathy.
This study determined whether performance in neurobehavioral tests deteriorates during subjectively annoying chemical challenge below known neurotoxic thresholds among persons with toxic encephalopathy with subjective hypersensitivity to chemicals. Subjects with symptoms and previous neuropsychological test results compatible with toxic encephalopathy (TE) of either type 2A (N=12) or 2B (N=12) and unexposed referents (N=12) were challenged in an exposure chamber. In a counterbalanced design, the subjects were exposed on 2 occasions to increasing air concentrations of n-butyl acetate and toluene at levels well below the thresholds for neurotoxic effects. Attention and motor speed tests were given (i) in room air outside the chamber before the challenge, (ii) in room air inside the chamber before the exposure, (iii) at 12 ppm (44 or 56 mg/m3), and (iv) at 48 ppm (at 180 or 228 mg/m3). For both substances the TE groups showed a slight increase (deterioration) in the simple reaction-time task during chemical exposure, but not in the complex reaction-time task or in the digit symbol test of the Wechsler Adult Intelligence Scale. Contrary to reference subjects, the TE subjects did not show any improvement or learning effect in the digit symbol test over the chamber phases. n-Butyl acetate tended to affect cognitive functioning more obviously than toluene did. Suggestion or expectancy effects were not observed in any group in the clean-air baseline conditions. The results do not support the notion that men with subjective hypersensitivity to chemicals would be more affected than healthy men regarding cognitive functioning during annoying solvent exposure below thresholds for acute neurotoxic effects.


Tailoring sparse multivariable regression techniques for prognostic single-nucleotide polymorphism signatures.
When seeking prognostic information for patients, modern technologies provide a huge amount of genomic measurements as a starting point. For single-nucleotide polymorphisms (SNPs), there may be more than one million covariates that need to be simultaneously considered with respect to a clinical endpoint. Although the underlying biological problem cannot be solved on the basis of clinical cohorts of only modest size, some important SNPs might still be identified. Sparse multivariable regression techniques have recently become available for automatically identifying prognostic molecular signatures that comprise relatively few covariates and provide reasonable prediction performance. For illustrating how such approaches can be adapted to the specific features of SNP data, we propose different variants of a component-wise likelihood-based boosting approach. The latter links SNP measurements to a time-to-event endpoint by a regression model that is built up in a large number of steps. The variants allow for strategic choices in dealing with SNPs that differ in variance because of their variation in minor allele frequencies. In addition, we propose a heuristic that allows computationally efficient handling of millions of covariates, thus opening the door for incorporating SNP × treatment interactions. We illustrate this using data from patients with acute myeloid leukemia. We judge the resulting models according to prediction error curves and using resampling data sets. We obtain increased stability by moving interpretation from the SNP to the gene level. By considering these different aspects, we outline a more general strategy for linking SNP measurements to a time-to-event endpoint by means of sparse multivariable regression models.


The African baobab (Adansonia digitata, Malvaceae): genetic resources in neglected populations of the Nuba Mountains, Sudan.
• Adansonia digitata L. is one of the most important indigenous fruit trees of mainland Africa. Despite its significance for subsistence and income generation of local communities, little is known about the genetic and morphological variability of East African populations of A. digitata, including those of Sudan. The aim of the current study, therefore, was to analyze genetic and morphological variability of different baobab populations in Kordofan, Sudan and to estimate the effect of human intervention on genetic differentiation and diversity.• A total of 306 trees were randomly sampled from seven spatially separated locations in the Nuba Mountains, Sudan, to cover a wide range of differing environmental gradients and management regimes ('homesteads' and 'wild'). Genetic analyses were conducted using nine microsatellite markers. Because of the tetraploid nature of A. digitata, different approaches were applied to estimate patterns of genetic diversity. Investigations were completed by measurements of dendrometric and fruit morphological characters.• Genetic diversity was balanced and did not differ between locations or management regimes, although tendencies of higher diversity in 'homesteads' were observed. A Bayesian cluster approach detected two distinct gene pools in the sample set, mainly caused by one highly diverse population close to a main road. The variability of tree characters and fruit morphometries was high, and significantly different between locations.• Results indicated a rather positive effect with human intervention. The observed populations provide a promising gene pool and likely comprise ecotypes well-adapted to environmental conditions at the northern distribution range of the species, which should be considered in conservation and management programs.


Maternal occupation and the risk of neural tube defects in offspring.
We evaluated the association between maternal occupation and the risk of neural tube defects (NTDs) in offspring. Data for 491 nonsyndromic cases were obtained from the Texas Birth Defects Registry for deliveries between 1999 and 2009. We randomly selected 2,291 controls among all live births in Texas during this time. Maternal occupations were classified using automated software and manual assignment. Multivariable logistic regression analyses were used to examine the relationship between maternal occupation and risk for any NTD, adjusting for maternal race/ethnicity, any diabetes, and maternal body mass index. These analyses were repeated for spina bifida specifically. Some maternal occupations, particularly those related to business/finance, health care practice, and cleaning/maintenance, were significantly associated with increased risk of spina bifida and/or any NTD. Further research is needed to identify the specific occupational exposures related to NTD risk.


Pre-dialysis application of the glucose infusion test for recirculation detection.
Vascular access recirculation (R) is a well-known cause of decreased dialysis dose. In this paper a new easy protocol for R detection in pre-dialysis derived from the classic Glucose Infusion Test (GIT) is introduced. The pre-dialysis GIT (GIT-pre) is based on the glucose (5%, 10 ml) bolus injection directly into the venous needle and on a simultaneous withdrawal from the arterial needle. If the glucose value increases during the glucose bolus, R is present. This new protocol was validated on 29 chronic haemodialysis patients (20 AVFs, 7 CVCs, 2 PTFE grafts), comparing the glucose increase with the classic GIT during dialysis. Only one CVC had R with the blood lines in the normal position (deltaglu = 465 mg/dl with GIT-pre and a deltaglu = 186 mg/dl, R = 9.3% with classic GIT) while in the reverse blood line position, all CVCs showed a significant glucose increase (mean GIT-pre deltaglu = 195 mg/dl; mean GIT deltaglu = 140 mg/dl corresponding to a R = 8%). There were 5 AVFs with true R (correct blood lines position) clearly identified by both methods (mean values deltaglu = 316 mg/dl with GIT-pre and a deltaglu = 390 mg/dl, R = 19.5% with classic GIT). Preliminary results show good reliability of the new protocol in identifying VA R caused either by failing VA with stenosis or by reverse blood lines position. The GIT-pre is a simpler application of the classic GIT useful for testing new VA, new needle positions or CVC performance before starting dialysis. A simpler R test could increase the frequency of the measurements and consequently the power of R in early detection of VA problems.


Creating national care standards for neonatal intensive care units in 2007.
Infant mortality rate was reported 3.18 in 1000 births in Iran. International organizations such as World Health Organization (WHO) and United Nations Children's Fund (UNICEF) consider applicable standards essential for providing effective health services in hospitals and health centers. Therefore, it is essential to create national care standards for neonatal intensive care units (NICU) in Iran. This was a multiple triangulation study conducted in 2007. In the first step, international standards were extracted from appropriate sites. Then, using Delphi method, as well as the viewpoints of 15 experts in clinical medical sciences, a set of suggested standards for intensive care unit was prepared. In the third step, 42 clinical science experts of Iran were selected, and their viewpoints on applicability of the suggested standards were investigated through a descriptive survey method. Data obtained in this step were analyzed using descriptive statistics. First, intensive care standards were extracted; then clinical science experts reviewed the suitability and applicability of suggested set of standards for Iran and finalized them. Finally, 386 standards for intensive care were drafted and approved by 77.5% to 100% desirability rate for NICUs of Iran. The findings of the study showed that most standards were either appropriate or fairly appropriate. So, necessary changes in final standards were made based on subjects, viewpoints and suggestions as well as the results of consulting with supervisors.


Prelytic and lytic conformations of erythrocyte-associated Escherichia coli hemolysin.
Flow cytometry was developed as a method to assess the conformation of erythrocyte-bound Escherichia coli hemolysin polypeptide (HlyA). Topology of membrane-associated hemolysin (HlyA(E)) was investigated by testing surface accessibility of HlyA regions in lytic and nonlytic bound states, using a panel of 12 anti-HlyA monoclonal antibodies (MAbs). Hemolysin associates nonlytically with erythrocytes at 0 to 2 degrees C. To test the hypothesis that the nonlytic HlyA(E) conformation at 0 to 2 degrees C differs from the lytic conformation at 23 degrees C, MAb epitope reactivity profiles at the two temperatures were compared by flow cytometry. Four MAbs have distinctly increased reactivity at 0 to 2 degrees C compared to 23 degrees C. HlyA requires HlyC-dependent acylation at lysine residues 563 and 689 for lytic function. Toxin with cysteine substitution mutations at each lysine (HlyA(K563C) and HlyA(K689C)) as well as the nonacylated form of hemolysin made in a HlyC-deficient strain were examined by flow cytometry at 0 to 2 and 23 degrees C. The three mutants bind erythrocytes at wild-type toxin levels, but there are conformational changes reflected by altered MAb epitope accessibility for six of the MAbs. To test further the surface accessibility of regions in the vicinity of MAb-reactive epitopes, HlyA(E) was proteolytically treated prior to testing for MAb reactivity. Differences in protease susceptibility at 0 to 2 degrees and 23 degrees C for the reactivities of three of the MAbs further support the model of two distinct conformations of cell-associated toxin.


A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1-p13.3.
Autosomal recessive inheritance of non-syndromic mental retardation (ARNSMR) may account for approximately 25% of all patients with non-specific mental retardation (NSMR). Although many X-linked genes have been identified as a cause of NSMR, only three autosomal genes are known to cause ARNSMR. We present here a large consanguineous Turkish family with four mentally retarded individuals from different branches of the family. Clinical tests showed cognitive impairment but no neurological, skeletal, and biochemical involvements. Genome-wide mapping using Human Mapping 10K Array showed a single positive locus with a parametric LOD score of 4.92 in a region on chromosome 1p21.1-p13.3. Further analyses using polymorphic microsatellite markers defined a 6.6-Mb critical region containing approximately 130 known genes. This locus is the fourth one linked to ARNSMR.


A study on the influence of Ni-Ti M-Wire in the flexural fatigue life of endodontic rotary files by using Finite Element Analysis.
The aim of this paper is to analyze the cyclic performance of two different Ni-Ti endodontic rotary files made from different alloys under bending using Finite Element Analysis (FEA). When experimentation is not available, this is not a trivial task and most papers on the subject rely on static analysis only. Two Ni-Ti rotary instruments are selected, ProFile GT and a GT Series X (GTX). The latter file is made from M-Wire, which has been thermo-mechanically processed to have larger flexibility, according to its manufacturer. The mechanical response was studied by considering different scenarios in the FEA package, in which the material properties were introduced according to existing literature. The method and results are presented and discussed so that this paper can be used as a guideline for future works. Although not fully reflective of the instrument's behavior in a dynamic rotation intra-canal system, the models used constitute a good approximation when a comparison between two instruments is at stake. It is shown that the GTX file has a lower risk of fatigue fracture during its clinical use when compared to the GT file, especially when the root canal makes the file deform into an extreme geometry. However, if the root canal does not make the file deform more than a certain amount, the GT file is equally good from the point of view of mechanical endurance.


Thermal Structure and Major Ion Composition of the Venus Ionosphere: First RPA Results from Venus Orbiter.
Thermal plasma quantities measured by, the retarding potential analyzer (RPA) are, together with companion Pioneer Venus measurements, the first in situ measurements of the Venus ionosphere. High ionospheric ion and electron temperatures imply significant solar wind heating of the ionosphere. Comparison of the measured altitude profiles of the dominant ions with an initial modlel indicates that the ionosphere is close to diffusive equilibrium. The ionopause height was observed to vary from 400 to 1000 kilometers in early orbits. The ionospheric particle pressure at the ionopause is apparently balanced at a solar zenith angle of about 70 degrees by the magnetic field pressure with little contribution from energetic solar wind particles. The measured ratio of ionospheric scale height to ionopause radius is consistent with that inferred from previously measured bow shock positions.


Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer.
We investigated quality and efficacy criteria of an autologous, physically and immunologically purified, Newcastle disease virus (NDV)-modified, irradiated tumor-cell vaccine (ATV-NDV) by analyzing three independent cohorts (a through c) of patients vaccinated between 1991 and 1995. Included were 63 patients with primary breast cancer (a), 27 with metastatic pretreated breast cancer (b), and 31 with metastatic pretreated ovarian cancer (c). In addition to vaccine, cohorts b and c received nonspecific immunotherapy as supportive treatment. After cryoconservation and purification, the vaccines varied in applied numbers of viable cells and dead cell contaminations. We retrospectively hypothesized that an immunogenic vaccine should contain at least 1.5 x 10(6) viable tumor cells and viability should be at least 33%. Each cohort was thus divided into two groups; one that received vaccine type A (A), fulfilling both criteria; and the other type B (B), missing one or both criteria. Conventional prognostic factors were wall balanced between A and B in cohorts a and c. In cohort a, there was a benefit in survival (P = .026) and disease-free survival (P = .089) for A. In addition, in cohort a, the relative risk of dying in the group that received A as compared with B was 0.2 (univariate Cox model). There were also survival trends in favor of A versus B (P = .18 and P = .09, respectively) in cohorts b and c, with relative risks of 0.5 and 0.42, respectively. In cohort b, the survival benefit could not be ascribed to vaccine quality alone, because of prognostic imbalance in favor of A. In cohort c, like in cohort a, the survival benefit for A may be ascribed to the ATV-NDV vaccine quality, since prognostic factors were not biased. This could imply clinical effectivity in breast and ovarian cancer with ATV-NDV high-quality vaccine. Furthermore, the data provide clinically relevant information for standardization and quality control of autologous tumor-cell vaccines. A randomized study is urgently needed.


Allogeneic hematopoietic cell transplantation for acute myeloid leukemia with hyperdiploid complex karyotype.
Allogeneic hematopoietic cell transplantation (allo-HCT) remains the best consolidation strategy for acute myeloid leukemia (AML) with complex karyotype (CK). However, CK is a heterogenous and highly diverse entity. Numerical abnormalities have been associated with a controversial prognosis and AML with only multiple numerical abnormalities known as pure hyperdiploid karyotype (HDK) may have a distinct prognosis after allo-HCT compared to non-pure HDK CK AML. A total of 236 patients were identified within the EBMT registry as having HDK comprising 95 pure (pHDK) and 141 with other cytogenetic abnormalities (HDK+). The 2-year probability of leukemia-free survival (LFS) was 50% for pHDK and 31% for HDK+ (p = 0.003). The 2-year probability of overall survival (OS) was 57% for pHDK and 36% for HDK+ (p = 0.007). The 2-year cumulative incidence of relapse (RI) was 22% for pHDK and 44% for HDK+ (p = 0.001). The 2-year probability of graft-versus-host disease (GvHD)-free and relapse-free survival (GRFS) was 36% for pHDK and 21% for HDK+ (p = 0.01). On multivariate analysis, pHDK remained associated with significantly better LFS, OS and GRFS and lower RI (all p-values <0.004). pHDK AML constitutes probably a distinct cytogenetic entity from HDK+ or other non-hyperdiploid CK AML with better outcomes after allo-HCT.


The role of email guidance in internet-based cognitive-behavioural self-care treatment for bulimia nervosa.
Email has been progressively used as a means for providing therapeutic guidance and support for cognitive behavioural treatment (CBT) self-care programmes. Many aspects of the use of email in self-care need to be explored such as the content of therapists' emails. Such information would optimise the delivery of self-care treatments. To date no study has looked at the content of the therapists' emails. We analysed the content of emails (n = 712) sent by therapists to participants (n = 71) of a randomised controlled trial (RCT) of internet-based CBT with email support for bulimic disorders. 14.7% of the emails therapists sent contained at least one CBT comment, while 95.4% had at least one supportive comment and 13.6% had at least one technical comment. The mean time spent on providing email support to each participant across the complete programme was 45 minutes. Emails sent by therapists were mainly supportive in content, with only a small amount of time being required by therapists to provide email support.


The treatment of venous malformations with percutaneous sclerotherapy at a single academic medical center.
We report a retrospective analysis of venous malformation patients treated with percutaneous sclerotherapy, describing their clinical manifestations, therapeutic outcomes and procedural complications. We reviewed our Vascular Anomalies database for all patients who underwent percutaneous sclerotherapy for venous malformation between January 2005 and July 2011 and retrieved 186 patients, out of which 116 were included in the final analysis. The majority of patients were treated using 100% alcohol (72%) and the rest were treated with <100% alcohol, Sodium Tetradecyl Sulfate or combination of these therapies. The most common location was the lower extremity in 67 patients (58%), followed by the head and neck in 27 (23%) and the upper extremity in 11 (9%). Retrospective review of medical records was performed. Outcomes were classified on an improvement scale based on clinical therapeutic effects. Two-hundred and forty-five sclerotherapy procedures were performed in 116 patients, of which 52 patients (45%) underwent a single procedure, 32 (28%) had two procedures and 32 (28%) underwent ≥3 procedures. Median follow-up period from the last procedure was 2.5 months (interquartile range of 2.0 to 6.75 months). Significant improvement was seen in 37 patients (32%), moderate improvement in 31 (27%), mild improvement in 20 (17%), no improvement in 21 (18%) and worse than before in 7 (6%) patients. Major post-procedural complications were nerve injuries in 6 patients (5%), deep vein thrombosis in 5 (4%), muscle contracture in 2 (2%), infection in 3 (3%), skin necrosis in 4 (3%) and other complications in 3 (3%). Our study demonstrated that 76% of our patients with venous malformation had some level of improvement in symptoms with majority (72%) undergoing only one or two percutaneous sclerotherapy procedure/s. Although major complications occurred in 20% of the patients, majority (74%) of the complications either resolved spontaneously or were successfully treated.


Accuracy of rib palpation for dry needling of deep periscapular musculature, measured with ultrasound.
Dry needling of the periscapular musculature is a procedure commonly performed by physical therapists. Needling of the deep musculature may be challenging, and use of a thoracic rib as a "backstop" is often applied to prevent inadvertent puncture of the pleura. The aim of this study was to: 1) To examine the accuracy rate of experienced physical therapists in identifying a mid-scapular thoracic rib using palpation, 2) to understand patient characteristics that affect the accuracy rate, and 3) to examine if therapist confidence levels were associated with palpatory accuracy. Two experienced physical therapists attempted to palpate a thoracic rib in the mid-scapular region of healthy participants (n = 101 subjects, 202 ribs), and self-reported their level of confidence in an accurate palpation. Their accuracy was verified with ultrasonography. The two physical therapists were accurate on 73.3% of palpations and did not differ in accuracy (72.0% vs. 75.0%, p = 0.747). The only ultrasonographic or subject characteristic measurement that correlated with improved accuracy was a reduced muscle thickness (p = 0.032). Therapists' self-reported confidence levels did not correlate to actual accuracy (p = 0.153). Physical therapists should be aware that palpation of a thoracic rib may not be as accurate as it may seem. The greater thickness of muscle in the area reduces the accuracy of accurate palpation. Dry needling of the periscapular muscles should be done with caution if using a rib as a "blocking" technique.


Comparative stem cell biology.
This review collates data from a range of stem cells studies in an attempt to bring together an overall view of stem cell biology. Data from hemopoietic, keratopoietic, hepatopoietic and neuropoietic stem cells are presented. The developmental and cell biology of each system is discussed in an attempt to develop a comparative view of stem cell biology. Comparisons are drawn in the areas of clonal analysis, surface antigen expression, adhesion molecules and cytokine interactions. Where appropriate the role of embryonic stem (ES) cells is also considered in the developmental biology of the cells in question.


Evaluation of the FASTPlaqueTB assay for direct detection of Mycobacterium tuberculosis in sputum specimens.
Sputum samples were collected from suspected tuberculosis patients attending out-patient clinics at the Ojha Institute of Chest Diseases, Karachi, Pakistan. To evaluate the performance of the FASTPlaqueTB assay for rapid diagnosis of pulmonary tuberculosis. A comparative study of 584 sputum samples using acid-fast smear microscopy, Lowenstein-Jensen culture and FASTPlaqueTB. A total of 514 samples yielded complete results. Seventy specimens were lost to analysis due to the overgrowth of contaminants. The addition of antimicrobials inhibited growth of gram-positive contaminants, and reduced the overall contamination rate from 18.2% to 7.2%. Mycobacterium tuberculosis was isolated from 175 smear-positive and 70 smear-negative specimens. FASTPlaqueTB detected M. tuberculosis in 81.6% of specimens, with a specificity of 97.7%. The sensitivity and specificity of the assay for smear-positive specimens were respectively 87.4% and 88.2%. For smear-negative specimens, the sensitivity of the assay was 67.1% and the specificity was 98.4%. The combined sensitivity of smear and FASTPlaqueTB for M. tuberculosis was 90%. Test results were available in 48 hours. FASTPlaqueTB is a sensitive and specific test for rapid diagnosis of pulmonary tuberculosis in high prevalence areas. The test is sensitive enough to confirm a large number of clinically suspected smear-negative cases and improve case finding.


Hyalinizing trabecular tumor of thyroid: does frozen section prevent unnecessarily aggressive operation? Six new cases and a literature review.
Fine-needle aspiration cytology (FNAC) is very accurate in detecting papillary thyroid carcinomas (PTCs). According to the Bethesda system for reporting thyroid cytopathology, the risk for malignancy is 97-99% when FNAC is used to diagnose PTC; the malignancy risk is 60-75% when FNAC results in suspected PTCs. The presence of hyalinizing trabecular tumor (HTT) of the thyroid can cause misdiagnosis because its cytological features mimic PTCs. However, the use of frozen section analysis can assist in the recognition of unique architecture features of HTT, and thus may help prevent the undertaking of an unnecessarily aggressive operation. We retrospectively reviewed all patients diagnosed with HTT by permanent histopathology from February 2009 to October 2013. After acquired agreement of the patients, we analyzed all data and reviewed another nine cases of HTT reported in the English-language medical literature to examine the efficacy of frozen section. There were six patients included in our research (5 women and 1 man), with an average age of 48.8 years. Using frozen section, four patients were diagnosed with HTT and two patients were misinterpreted as PTC. Consequently, four patients had lobectomy and two patients had total thyroidectomy, with no surgical complications. Of the nine cases of HTT reviewed from the English literature, the use of frozen section showed three HTT cases, three PTC cases, two medullary thyroid carcinoma cases, and one deferral case. Overall, the use of frozen section as a diagnostic method prevented additional surgical resection in eight patients (53%). Frozen section can sometimes but not always be used to diagnose HTT. When HTT is diagnosed by its trabecular pattern through the use of frozen section, it may prevent total thyroidectomy.


Environmental toxicity, nutrition, and gene interactions in the development of atherosclerosis.
There is substantial evidence from epidemiological studies that the pathology of cardiovascular diseases is linked in part to environmental pollution. Many environmental contaminants, and especially persistent organic pollutants, are risk factors for atherosclerosis because they may exacerbate an underlying disease by altering gene expression patterns. Many mechanisms and signaling pathways associated with the pathology of "modern" diseases are similarly modulated by poor dietary habits and environmental pollutants. Many genes induced in diseases associated with vascular dysfunction such as atherosclerosis are oxidative stress-sensitive, suggesting that an imbalance in cellular oxidative stress and antioxidant status is a critical underlying factor. One of the emerging issues in modern toxicological sciences is the modification of environmental toxicity by nutrients. Evidence is emerging which suggests that antioxidant nutrients and related bioactive compounds common in fruits and vegetables protect against environmental toxic insult to the vascular endothelium by down-regulation of signaling pathways involved in inflammatory responses associated with vascular diseases such as atherosclerosis. Thus, the concept that nutrition may modify or ameliorate the toxicity of environmental chemicals may have implications for understanding the complex interaction of environmental toxicity and disease development.


Effect-based assessment of toxicity removal during wastewater treatment.
Wastewaters contain complex mixtures of chemicals, which can cause adverse toxic effects in the receiving environment. In the present study, the toxicity removal during wastewater treatment at seven municipal wastewater treatment plants (WWTPs) was investigated using an effect-based approach. A battery of eight bioassays was applied comprising of cytotoxicity, genotoxicity, endocrine disruption and fish embryo toxicity assays. Human cell-based CALUX assays, transgenic larval models and the fish embryo toxicity test were particularly sensitive to WWTP effluents. The results indicate that most effects were significantly reduced or completely removed during wastewater treatment (76-100%), while embryo toxicity, estrogenic activity and thyroid disruption were still detectable in the effluents suggesting that some harmful substances remain after treatment. The responsiveness of the bioassays was compared and the human cell-based CALUX assays showed highest responsiveness in the samples. Additionally, the fish embryo toxicity test and the transgenic larval models for endocrine disrupting effects showed high responsiveness at low sample concentrations in nearly all of the effluent samples. The results showed a similar effect pattern among all WWTPs investigated, indicating that the wastewater composition could be rather similar at different locations. There were no considerable differences in the toxicity removal efficiencies of the treatment plants and no correlation was observed with WWTP characteristics, such as process configuration or sludge age. This study demonstrated that a biotest battery comprising of multiple endpoints can serve as a powerful tool when assessing water quality or water treatment efficiency in a holistic manner. Rather than analyzing the concentrations of a few selected chemicals, bioassays can be used to complement traditional methods of monitoring in the future by assessing sum-parameter based effects, such as mixture effects, and tackling chemicals that are present at concentrations below chemical analytical detection limits.


Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001-2013: a Clinical Practice Research Datalink study.
Objective Trends in recorded diagnoses of chronic fatigue syndrome (CFS, also known as 'myalgic encephalomyelitis' (ME)) and fibromyalgia (FM) in the UK were last reported more than ten years ago, for the period 1990-2001. Our aim was to analyse trends in incident diagnoses of CFS/ME and FM for the period 2001-2013, and to investigate whether incidence might vary by index of multiple deprivation (IMD) score. Design Electronic health records cohort study. Setting NHS primary care practices in the UK. Participants Participants: Patients registered with general practices linked to the Clinical Practice Research Datalink (CPRD) primary care database from January 2001 to December 2013. Main outcome measure Incidence of CFS/ME, FM, post-viral fatigue syndrome (PVFS), and asthenia/debility. Results The overall annual incidence of recorded cases of CFS/ME was 14.8 (95% CI 14.5, 15.1) per 100,000 people. Overall annual incidence per 100,000 people for FM was 33.3 (32.8-33.8), for PVFS 12.2 (11.9, 12.5), and for asthenia/debility 7.0 (6.8, 7.2). Annual incidence rates for CFS/ME diagnoses decreased from 17.5 (16.1, 18.9) in 2001 to 12.6 (11.5, 13.8) in 2013 (annual percent change -2.8% (-3.6%, -2.0%)). Annual incidence rates for FM diagnoses decreased from 32.3 (30.4, 34.3) to 27.1 (25.5, 28.6) in 2007, then increased to 38.2 (36.3, 40.1) per 100,000 people in 2013. Overall annual incidence of recorded fatigue symptoms was 2246 (2242, 2250) per 100,000 people. Compared with the least deprived IMD quintile, incidence of CFS/ME in the most deprived quintile was 39% lower (incidence rate ratio (IRR) 0.61 (0.50, 0.75)), whereas rates of FM were 40% higher (IRR 1.40 (0.95, 2.06)). Conclusion These analyses suggest a gradual decline in recorded diagnoses of CFS/ME since 2001, and an increase in diagnoses of fibromyalgia, with opposing socioeconomic patterns of lower rates of CFS/ME diagnoses in the poorest areas compared with higher rates of FM diagnoses.


Determining water content in human nails with a portable near-infrared spectrometer.
The water content of human nail plates was determined using a portable near-infrared (NIR) spectrometer with an InGaAs photodiode array detector. NIR diffuse reflectance (DR) spectra were collected from 108 cut nail plates with different relative humidity and in vivo from fingernails. Partial least-squares (PLS) regression was applied to the NIR spectra in the 1115-1645 nm region to develop calibration models that determine the water content in the cut nail plates and fingernails. A good correlation was obtained between the NIR spectra and the water content measured by nuclear magnetic resonance (NMR) for the NIR measurement of both cut nail plates and fingernails. The results indicate that the water content in the nails can be determined very rapidly (1 s) by means of the portable NIR spectrometer and PLS regression.


A feasible strategy for preventing blood clots in critically ill patients with acute kidney injury (FBI): study protocol for a randomized controlled trial.
Previous pharmacokinetic trials suggested that 40 mg subcutaneous enoxaparin once daily provided inadequate thromboprophylaxis for intensive care unit patients. Critically ill patients with acute kidney injury are at increased risk of venous thromboembolism and yet are often excluded from these trials. We hypothesized that for critically ill patients with acute kidney injury receiving continuous renal replacement therapy, a dose of 1 mg/kg enoxaparin subcutaneously once daily would improve thromboprophylaxis without increasing the risk of bleeding. In addition, we seek to utilize urine output prior to discontinuing dialysis, and low neutrophil gelatinase-associated lipocalin in dialysis-free intervals, as markers of renal recovery. In a multicenter, double-blind randomized controlled trial in progress at three intensive care units across Denmark, we randomly assign eligible critically ill adults with acute kidney injury into a treatment (1 mg/kg enoxaparin subcutaneously once daily) or control arm (40 mg enoxaparin subcutaneously once daily) upon commencement of continuous renal replacement therapy.We calculated that with 133 patients in each group, the study would have 80% power to show a 40% reduction in the relative risk of venous thromboembolism with 1 mg/kg enoxaparin, at a two-sided alpha level of 0.05. An interim analysis will be conducted after the first 67 patients have been included in each group.Enrolment began in March 2013, and will continue for two years. The primary outcome is the occurrence of venous thromboembolism. Secondary outcomes include anti-factor Xa activity, bleeding, heparin-induced thrombocytopenia, filter lifespan, length of stay, ventilator free days, and mortality. We will also monitor neutrophil gelatinase-associated lipocalin and urine volume to determine whether they can be used as prognostic factors for renal recovery. Critically ill unit patients with acute kidney injury present a particular challenge in the provision of thromboprophylaxis. This study hopes to add to the growing evidence that the existing recommendation of 40 mg enoxaparin is inadequate and that 1 mg/kg is both safe and effective for thromboprophylaxis.In addition, the study seeks to identify predictors of renal recovery allowing for the proper utilization of resources. EU Clinical Trials Register: EudraCT number: 2012-004368-23, 25 September 2012.


Mapping the Transcriptional and Fitness Landscapes of a Pathogenic E. coli Strain: The Effects of Organic Acid Stress under Aerobic and Anaerobic Conditions.
Several methods are available to probe cellular responses to external stresses at the whole genome level. RNAseq can be used to measure changes in expression of all genes following exposure to stress, but gives no information about the contribution of these genes to an organism's ability to survive the stress. The relative contribution of each non-essential gene in the genome to the fitness of the organism under stress can be obtained using methods that use sequencing to estimate the frequencies of members of a dense transposon library grown under different conditions, for example by transposon-directed insertion sequencing (TraDIS). These two methods thus probe different aspects of the underlying biology of the organism. We were interested to determine the extent to which the data from these two methods converge on related genes and pathways. To do this, we looked at a combination of biologically meaningful stresses. The human gut contains different organic short-chain fatty acids (SCFAs) produced by fermentation of carbon compounds, and Escherichia coli is exposed to these in its passage through the gut. Their effect is likely to depend on both the ambient pH and the level of oxygen present. We, therefore, generated RNAseq and TraDIS data on a uropathogenic E. coli strain grown at either pH 7 or pH 5.5 in the presence or absence of three SCFAs (acetic, propionic and butyric), either aerobically or anaerobically. Our analysis identifies both known and novel pathways as being likely to be important under these conditions. There is no simple correlation between gene expression and fitness, but we found a significant overlap in KEGG pathways that are predicted to be enriched following analysis of the data from the two methods, and the majority of these showed a fitness signature that would be predicted from the gene expression data, assuming expression to be adaptive. Genes which are not in the E. coli core genome were found to be particularly likely to show a positive correlation between level of expression and contribution to fitness.


[Changes in the lungs in radiation treatment of head and neck tumors].
A study was made of the roentgenomorphological and roentgenofunctional appearance of pulmonary lesions in 120 patients with head and neck tumors during radiation therapy. Laryngeal cancer was diagnosed in 56 patients, cancer of the oral cavity in 48, and neck tumors in 16 patients. X-ray examination was done 1 month before and after the termination of gamma-beam radiotherapy, the summary focal doses varying from 40 to 75 Gy. The chief modes of lung examination were roentgenography and roentgenopneumopolygraphy. It was established that even before treatment the patients had latent signs of respiratory insufficiency. Radiotherapy, irrespective of the summary focal dose value, had a mediated effect on the lungs. One month after the discontinuation of radiotherapy the pulmonary pattern changed: its elements were enhanced and dilated, the general biomechanism of respiration impaired, particularly at the expense of reducing the respiratory mobility of the diaphragm and mediastinum, disorders of the bronchopulmonary ventilation increased. A multimodality x-ray study including roentgenopneumopolygraphy helps to detect in time regional disorders of lung function which is very important for prevention of lung complications.


Behavioral development in the absence of neural activity: effects of chronic immobilization on amphibian embryos.
Embryos of Xenopus laevis and Ambystoma mexicanum were continually immobilized from premotile stages of development to stages at which normally reared embryos were swimming well. Immobilization was achieved through exposure to solutions of chloretone, lidocaine, or alpha-bungarotoxin. At a number of stages after recovery from the drugs, spontaneous and stimulated behaviors were extensively quantified. Immobilization of Ambystoma embryos resulted in temporary defects in musculoskeletal development. In contrast, treated Xenopus embryos could not be distinguished from controls by simple visual observation within minutes to hours after removal from the drug solutions. Quantifications of behavior revealed, however, a transient period of 24-48 hr during which treated embryos exhibited consistently reduced measures of stimulated swimming, while showing an increase in frequency of spontaneous movements. Detailed behavioral testing could detect no permanent effects of chronic immobilization in either species after this initial period of recovery. The results are discussed in reference to the classic works of Harrison (1904), Carmichael (1926, 1927), and Matthews and Detwiler (1926).


Proclivity to self-injurious behavior in MRL-lpr mice: implications for autoimmunity-induced damage in the dopaminergic system.
Systemic lupus erythematosus is frequently accompanied by psychiatric manifestations of unknown origin. Although damage of central neurons had been documented, little is known about neurotransmitter systems affected by the autoimmune/inflammatory process. Recent studies on lupus-prone MRL-lpr mice point to imbalanced dopamine function and neurodegeneration in dopamine-rich brain regions. We follow up on anecdotal observations of singly housed mice developing chest wounds. Compulsive grooming and/or skin biting accounted for open lesions, lending itself to the operational term 'self-injurious behavior' (SIB). Low incidence of spontaneous SIB increased significantly after repeated injections of dopamine-2/3 receptor (D2/D3R) agonist quinpirole (QNP). To further probe the dopaminergic circuitry and examine whether SIB is associated with development of lupus-like disease, we compared behavioral responses among cohorts that differed in the immune status. Two-week treatment with QNP (intraperitoneal, 0.5 mg kg(-1) body weight per day) induced SIB in 60% of diseased MRL-lpr mice, and exacerbated their splenomegaly. Although increased grooming and stereotypy were observed in less symptomatic MRL+/+ controls, only one mouse (10%) developed SIB. Similarly, SIB was not seen in young, asymptomatic groups despite dissimilar ambulatory responses to QNP. In situ hybridization revealed treatment-independent upregulation of D2R mRNA in substantia nigra of diseased MRL-lpr mice. The above results suggest that development of systemic autoimmunity alters sensitivity of the dopaminergic system and renders MRL-lpr mice prone to SIB. Although pathogenic factors were not examined, we hypothesize that immune and endocrine mechanisms jointly contribute to early neuronal damage, which underlies behavioral deficiency in the adulthood.


A new scenario of plastid evolution: plastid primary endosymbiosis before the divergence of the "Plantae," emended.
A recent hypothesis on the origin of eukaryotic phototrophs proposes that red algae, green plants (land plants plus green algae), and glaucophytes constitute the primary photosynthetic eukaryotes, whose plastids may have originated directly from a cyanobacterium-like prokaryote via primary endosymbiosis, whereas the plastids of other lineages of eukaryotic phototrophs appear to be the result of secondary endosymbiotic events involving a phototrophic eukaryote and a host cell. However, the phylogenetic relationships among the three lineages of primary photosynthetic eukaryotes remained unresolved because previous nuclear multigene phylogenies used incomplete red algal gene sequences derived mainly from Porphyra (Rhodophyceae, one of the two lineages of the Rhodophyta), and lacked sequences from the Cyanidiophyceae (the other red algal lineage). Recently, the complete nuclear genome sequences from the red alga Cyanidioschyzon merolae 10D of the Cyanidiophyceae were determined. Using this genomic information, nuclear multigene phylogenetic analyses of various lineages of mitochondrion-containing eukaryotes were conducted. Since bacterial and amitochondrial eukaryotic genes present serious problems to eukaryotic phylogenies, basal eukaryotes were deduced based on the paralogous comparison of the concatenated alpha- and beta-tubulin. The comparison demonstrated that cellular slime molds (Amoebozoa) represent the most basal position within the mitochondrion-containing organisms. With the cellular slime molds as the outgroup, phylogenetic analyses based on a 1,525-amino acid sequence of four concatenated nuclear genes [actin, elongation factor-1alpha( EF-1alpha), alpha-tubulin, and beta-tubulin] resolved the presence of two large, robust monophyletic groups and the basal eukaryotic lineages (Amoebozoa). One of the two groups corresponded to the Opisthokonta (Metazoa and Fungi), whereas the other included various lineages containing primary and secondary plastids (red algae, green plants, glaucophytes, euglenoids, heterokonts, and apicomplexans), Ciliophora, Kinetoplastida, dinoflagellates, and Heterolobosea, for which the red algae represented the most basal lineage. Therefore, the plastid primary endosymbiosis likely occurred once in the common ancestor of the latter group, and the primary plastids were subsequently lost in the ancestor(s) of organisms within the group that now lacks primary plastids. A new concept of Plantae was proposed for phototrophic and nonphototrophic organisms belonging to this group on the basis of their common history of plastid primary endosymbiosis. This new scenario of plastid evolution is discussed here, and is compared with recent genome information and findings on the secondary endosymbiosis of the Euglena plastid.


Cytologic diagnosis and grading of ductal carcinoma in situ.
Fine-needle aspiration cytology plays an important role in the preoperative diagnosis of palpable masses as well as impalpable lesions that can only be sampled by stereotactic or ultrasound techniques. A further refinement of cytologic diagnosis would be the ability to distinguish among the different types of ductal carcinoma in situ (DCIS) also between in situ and invasive malignant disease. Sixty-six cases of histologically proven, pure DCIS (39 high grade, 12 cribriform, and 15 low/intermediate grade) with a preoperative cytology report of carcinoma were retrieved from our files. All the cytology (wet-fixed and air-dried smears) was reviewed by G.M., and the histology sections were reviewed by G.T. Seven cytologic features, including cellularity, cell dissociation, nuclear size, cell uniformity, nucleoli, nuclear margins, and chromatin pattern, were assigned scores from 1 to 3. The presence of calcium, necrosis, and foamy macrophages was recorded. Cell clusters were examined for evidence of a cribriform pattern. Fat and stromal fragments were closely checked for infiltration by tumor cells. The cell type was predominantly large and pleomorphic in high grade DCIS, whereas it was mainly small and well differentiated in the cribriform and low grade types. Calcium and necrosis were seen in most high grade lesions and less frequently in the cribriform and low grade ones. Macrophages were more common in high grade and cribriform DCIS than in low/intermediate grade DCIS. Cribriform spaces were noted only in cribriform DCIS. Stromal and fat infiltration by tumor cells was not present in any of the aspirates. Myoepithelial cells were rarely seen. The presence of pleomorphic carcinoma cells, calcium, necrosis, and macrophages in the aspirate accompanied by "casting" calcification on the mammogram is virtually diagnostic of high grade (comedo) DCIS. Cribriform DCIS shows features of low grade carcinoma with a typical cribriform pattern of punched-out holes in the cell clusters. Low/intermediate grade DCIS has no particular distinguishing features. Cancer (Cancer Cytopathol)


What implies the good work for registered nurses in municipal elderly care in Sweden?
The aim was to describe registered nurses' perceptions of what the good work implies to them in municipal elderly care. A descriptive design and a structured questionnaire specifically designed for this study were used. Sixty housing units for older people and 213 nurses participated, with a response rate of 62%. The good work included the following aspects: intellectually stimulating without guilt feelings; freedom and independence with the possibility to influence; having appreciative and pleasant fellow workers and a fair and understanding manager; a good physical and risk-free environment; work security and a steady income with the possibility of improving salary through work effort; work effort should be beneficial to others; innovative thinking and initiative should be highly valued; and pride in work without compromising personal values. Employers must take this into consideration to retain those nurses already employed and recruit nurses to municipal elderly care.


Fetal-specific forms of alpha 1-protease inhibitors in mouse plasma.
Adult mouse plasma contains two distinct alpha 1-protease inhibitors (alpha 1-PIs), which we have called alpha 1-PI(E) and alpha 1-PI(T) because of their differing specificities for elastase and trypsin. Plasma levels of the two mouse inhibitors, determined either functionally or immunologically, are lower in fetal animals than in adults. Western blotting after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, using specific, polyclonal antibodies raised to the inhibitors in adult plasma shows new immunoreactive species of both alpha 1-PI(T) and alpha 1-PI(E) in fetal mouse plasma with apparent molecular weights approximately 1 kDa less than the corresponding proteins in adult plasma. In both cases the fetal alpha 1-PI is replaced by the adult protein between 2 and 6 days after birth. After chemical deglycosylation, the molecular weight difference between the adult and fetal forms of alpha 1-PI(E) and alpha 1-PI(T) is retained, suggesting that the adult and fetal mouse alpha 1-PIs have different amino acid sequences. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the protease inhibitors, cleaved specifically at the protease binding site, indicated that the difference in sequence between the adult and fetal proteins resided in the 50-60 kDa N-terminal fragment.


Modeling of the metallic port in breast tissue expanders for photon radiotherapy.
The purpose of this study was to model the metallic port in breast tissue expanders and to improve the accuracy of dose calculations in a commercial photon treatment planning system (TPS). The density of the model was determined by comparing TPS calculations and ion chamber (IC) measurements. The model was further validated and compared with two widely used clinical models by using a simplified anthropomorphic phantom and thermoluminescent dosimeters (TLD) measurements. Dose perturbations and target coverage for a single postmastectomy radiotherapy (PMRT) patient were also evaluated. The dimensions of the metallic port model were determined to be 1.75 cm in diameter and 5 mm in thickness. The density of the port was adjusted to be 7.5 g/cm3 which minimized the differences between IC measurements and TPS calculations. Using the simplified anthropomorphic phantom, we found the TPS calculated point doses based on the new model were in agreement with TLD measurements within 5.0% and were more accurate than doses calculated based on the clinical models. Based on the photon treatment plans for a real patient, we found that the metallic port has a negligible dosimetric impact on chest wall, while the port introduced significant dose shadow in skin area. The current clinical port models either overestimate or underestimate the attenuation from the metallic port, and the dose perturbation depends on the plan and the model in a complex way. TPS calculations based on our model of the metallic port showed good agreement with measurements for all cases. This new model could improve the accuracy of dose calculations for PMRT patients who have temporary tissue expanders implanted during radiotherapy and could potentially reduce the risk of complications after the treatment.


Infant feeding and contraceptive practices among adolescents with a high teen pregnancy rate: a 3-year retrospective study.
Adolescents consistently demonstrate the lowest rates of breastfeeding among women of reproductive age despite well-documented benefits of breastfeeding. In Amarillo, Texas, a medium-sized community with a perennially high teen pregnancy rate, we sought (1) to determine breastfeedings practices among adolescent females immediately after delivery and again at 6 weeks and (2) to identify contraceptive choices among the same teen population. This was a retrospective chart review focused on adolescents between the ages of 13 and 18 coming to a university-based obstetrical service between January 1, 2006, and December 31, 2008. Data on breastfeeding and contraceptive practices were analyzed. Five hundred forty-three cases were analyzed. At hospital discharge, 59.3% initiated breastfeeding, but this dropped to 22.2% at the 6-week postpartum appointment. Over 27% of all study subjects failed to appear for postpartum evaluation. Multiparity was the only outcome variable associated with failure to initiate breastfeeding. Depot-medroxyprogesterone acetate, the levonorgestrel intrauterine device (IUD), and combination oral contraceptives were the most popular contraceptive choices, but 16% elected to forego any form of contraception at the postpartum visit. Adolescent women living in an area of Texas with a high teen pregnancy rate reported relatively low breastfeeding rates immediately postpartum, with a >50% decrease in breastfeeding in any form by 6 weeks postpartum. A substantial number failed to initiate any form of contraception at the postpartum visit. These findings support the critical need for additional breastfeeding support and contraceptive education in this at-risk adolescent population.


Treatment of hypertension in the very old.
The objective of this study was to compare the long-term efficacy and safety of 6 months' treatment with barnidipine and hydrochlorothiazide (HCTZ) as monotherapy in patients aged > or = 75 years with mild to moderate essential hypertension. This was a randomised, double-blind, dose-titration study performed at 62 centres in 8 countries. A total of 397 patients were enrolled. Following a 4 week single-blind placebo runin, 315 patients with a sitting diastolic blood pressure (SiDBP) of 95-115 mmHg and a systolic blood pressure of 150-200 mmHg were randomised to receive barnidipine 10 mg (n = 159) or HCTZ 12.5 mg (n = 155) once daily. In patients who had not responded (SiDBP > 90 mmHg) after 6 weeks of double-blind treatment, the dose was titrated upwards to barnidipine 20 mg or HCTZ 25 mg. After 18 weeks, those who did not respond to the higher dose had enalapril (up to 10 mg once daily) added to their regimen. Statistically equivalent reductions in SiDBP were achieved with barnidipine and HCTZ monotherapy. At week 18 of double-blind treatment on monotherapy, 84% of patients in both groups were responders. The addition of enalapril in non-responders produced a further reduction in blood pressure. Both drugs were well tolerated. The incidence of drug-related adverse events was greater in the barnidipine than HCTZ-treated group but they were consistent with vasodilation and were categorised as mild to moderate. In conclusion, barnidipine and HCTZ are well tolerated and have equivalent long-term antihypertensive efficacy in older hypertensive patients. For patients whose blood pressure is inadequately controlled on monotherapy, combination therapy with enalapril is effective.


A Novel Method for Determination of Methadone in the Serum by High-Performance Liquid Chromatography with Electrochemical Detection.
In March 2013, the clinical use of oral methadone tablets was initiated in Japan. There are many factors responsible for the change in blood concentrations of methadone, and its pharmacokinetics is very complex. Therefore, a simple and accurate measurement method for methadone blood concentrations was developed using HPLC/electrochemical detector (ECD). An eluent of 10 mM Na2HPO4/CH3CN/CH3OH (20 : 19 : 3) was used as the mobile phase. The column was used the XTerra® RP18, and the voltage of the ECD was set at 400 to 800 mV. As a result, the calibration curve was linear in the ranges of 10 to 100 ng/mL (y=5012.7x+1041.1, r=0.999). The intra- and inter-day coefficients of variation were <5.2 and <5.8%, respectively. Therefore, this method was considered to be useful for the measurement of methadone blood levels in cancer patients. Also, using this method, blood methadone concentration was measured over time in a patient with cancer-associated pain who was treated with methadone. The estimated clearance (CL/F) and distribution volume (Vd/F) of methadone were 2.84 L/h and 502.8 L, respectively, and took about two weeks to reach steady state.


Hereditary hydrocephalus in laboratory-reared golden hamsters (Mesocricetus auratus).
A colony of golden hamsters had an ongoing problem with hydrocephalus. In an attempt to clear the colony of the problem, new breeders from another supplier had been purchased. At termination of a behavioral study, the brain was collected from 35 animals (four of which had died with hydrocephalus during the study) and was examined macroscopically and by light microscopy. Although no animals manifested obvious behavioral changes, 31 of 35 (88.6%, 13/15 males and 18/20 females in control and manipulated groups) had hydrocephalus. Twenty-five animals had macroscopically identifiable hydrocephalus, and six had hydrocephalus identified microscopically. Neither teratogenic concentrations of metals nor mycotoxins were detected in tissues or food, and sera from breeders tested negative for antibodies to Sendai virus, reovirus 3, and lymphocytic choriomeningitis virus. Trial matings of breeders expected to produce hydrocephalic offspring resulted in affected offspring, and mating of breeders expected to produce normal offspring resulted in normal or less-affected offspring. Hydrocephalus was confirmed retrospectively in some breeders. Hereditary hydrocephalus appears to be widespread in hamster stocks in Central Europe. Affected animals do not manifest signs of disease and usually die without obvious premonitory signs. Despite severe hydrocephalus, the animals can breed, and animal handlers do not identify motor deficits or abnormal behavioral activity. This entity is unlike the previously described, hereditary hydrocephalus of hamsters that is phenotypically identifiable and usually is lethal before they attain breeding age.


PI3Kgamma protects from myocardial ischemia and reperfusion injury through a kinase-independent pathway.
PI3Kgamma functions in the immune compartment to promote inflammation in response to G-protein-coupled receptor (GPCR) agonists and PI3Kgamma also acts within the heart itself both as a negative regulator of cardiac contractility and as a pro-survival factor. Thus, PI3Kgamma has the potential to both promote and limit M I/R injury. Complete PI3Kgamma-/- mutant mice, catalytically inactive PI3KgammaKD/KD (KD) knock-in mice, and control wild type (WT) mice were subjected to in vivo myocardial ischemia and reperfusion (M I/R) injury. Additionally, bone-marrow chimeric mice were constructed to elucidate the contribution of the inflammatory response to cardiac damage. PI3Kgamma-/- mice exhibited a significantly increased infarction size following reperfusion. Mechanistically, PI3Kgamma is required for activation of the Reperfusion Injury Salvage Kinase (RISK) pathway (AKT/ERK1/2) and regulates phospholamban phosphorylation in the acute injury response. Using bone marrow chimeras, the cardioprotective role of PI3Kgamma was mapped to non-haematopoietic cells. Importantly, this massive increase in M I/R injury in PI3Kgamma-/- mice was rescued in PI3Kgamma kinase-dead (PI3KgammaKD/KD) knock-in mice. However, PI3KgammaKD/KD mice exhibited a cardiac injury similar to wild type animals, suggesting that specific blockade of PI3Kgamma catalytic activity has no beneficial effects. Our data show that PI3Kgamma is cardioprotective during M I/R injury independent of its catalytic kinase activity and that loss of PI3Kgamma function in the hematopoietic compartment does not affect disease outcome. Thus, clinical development of specific PI3Kgamma blockers should proceed with caution.


Meaningful Use of an Electronic Health Record in the New York City Jail System.
Use of electronic health records (EHRs) is an important innovation for patients in jails and prisons. Efforts to incentivize health information technology, including the Medicaid EHR Incentive Program, are generally aimed at community providers; however, recent regulation changes allow participation of jail health providers. In the New York City jail system, the Department of Health and Mental Hygiene oversees care delivery and was able to participate in and earn incentives through the Medicaid EHR Incentive Program. Despite the challenges of this program and other health information innovations, participation by correctional health services can generate financial assistance and useful frameworks to guide these efforts. Policymakers will need to consider the specific challenges of implementing these programs in correctional settings.


Effect of a Community-Based Service Learning Experience in Geriatrics on Internal Medicine Residents and Community Participants.
Community-based service learning (CBSL) provides an opportunity to teach internal medicine residents the social context of aging and clinical concepts. The objectives of the current study were to demonstrate the feasibility of a CBSL program targeting internal medicine residents and to assess its effect on medical residents and community participants. internal medicine residents participated in a CBSL experience for half a day during ambulatory blocks from 2011 to 2014. Residents attended a senior housing unit or center, delivered a presentation about a geriatric health topic, toured the facility, and received information about local older adult resources. Residents evaluated the experience. Postgraduate Year 3 internal medicine residents (n = 71) delivered 64 sessions. Residents felt that the experience increased their ability to communicate effectively with older adults (mean 3.91 ± 0.73 on a Likert scale with 5 = strongly agree), increased their knowledge of resources (4.09 ± 1.01), expanded their knowledge of a health topic pertinent to aging (3.48 ± 1.09), and contributed to their capacity to evaluate and care for older adults (3.84 ± 0.67). Free-text responses demonstrated that residents thought that this program would change their practice. Of 815 older adults surveyed from 36 discrete teaching sessions, 461 (56%) thought that the medical residents delivered health information clearly (4.55 ± 0.88) and that the health topics were relevant (4.26 ± 0.92). Free-text responses showed that the program helped them understand their health concerns. This CBSL program is a feasible and effective tool for teaching internal medicine residents and older adults.


Electroencephalographic Correlate of Mexican Spanish Emotional Speech Processing in Autism Spectrum Disorder: To a Social Story and Robot-Based Intervention.
Socio-emotional impairments are key symptoms of Autism Spectrum Disorders. This work proposes to analyze the neuronal activity related to the discrimination of emotional prosodies in autistic children (aged 9 to 11-year-old) as follows. Firstly, a database for single words uttered in Mexican Spanish by males, females, and children will be created. Then, optimal acoustic features for emotion characterization will be extracted, followed of a cubic kernel function Support Vector Machine (SVM) in order to validate the speech corpus. As a result, human-specific acoustic properties of emotional voice signals will be identified. Secondly, those identified acoustic properties will be modified to synthesize the recorded human emotional voices. Thirdly, both human and synthesized utterances will be used to study the electroencephalographic correlate of affective prosody processing in typically developed and autistic children. Finally, and on the basis of the outcomes, synthesized voice-enhanced environments will be created to develop an intervention based on social-robot and Social StoryTM for autistic children to improve affective prosodies discrimination. This protocol has been registered at BioMed Central under the following number: ISRCTN18117434.


Cost Dynamics of Clean Energy Technologies.
The pace of the global decarbonization process is widely believed to hinge on the rate of cost improvements for clean energy technologies, in particular renewable power and energy storage. This paper adopts the classical learning-by-doing framework of Wright (1936), which predicts that cost will fall as a function of the cumulative volume of past deployments. We first examine the learning curves for solar photovoltaic modules, wind turbines and electrolyzers. These estimates then become the basis for estimating the dynamics of the life-cycle cost of generating the corresponding clean energy, i.e., electricity from solar and wind power as well as hydrogen. Our calculations point to significant and sustained learning curves, which, in some contexts, predict a much more rapid cost decline than suggested by the traditional 80% learning curve. Finally, we argue that the observed learning curves for individual clean energy technologies reinforce each other in advancing the transition to a decarbonized energy economy.


Experimental and Computational Studies on the Scattering of an Edge-Guided Wave by a Hidden Crack on a Racecourse Shaped Hole.
Reliable and quantitative non-destructive evaluation for small fatigue cracks, in particular those in hard-to-inspect locations, is a challenging problem. Guided waves are advantageous for structural health monitoring due to their slow geometrical decay of amplitude with propagating distance, which is ideal for rapid wide-area inspection. This paper presents a 3D laser vibrometry experimental and finite element analysis of the interaction between an edge-guided wave and a small through-thickness hidden edge crack on a racecourse shaped hole that occurs, in practice, as a fuel vent hole. A piezoelectric transducer is bonded on the straight edge of the hole to generate the incident wave. The excitation signal consists of a 5.5 cycle Hann-windowed tone burst of centre frequency 220 kHz, which is below the cut-off frequency for the first order Lamb wave modes (SH1). Two-dimensional fast Fourier transformation (2D FFT) is applied to the incident and scattered wave field along radial lines emanating from the crack mouth, so as to identify the wave modes and determine their angular variation and amplitude. It is shown experimentally and computationally that mid-plane symmetric edge waves can travel around the hole's edge to detect a hidden crack. Furthermore, the scattered wave field due to a small crack length, a, (compared to the wavelength λ of the incident wave) is shown to be equivalent to a point source consisting of a particular combination of body-force doublets. It is found that the amplitude of the scattered field increases quadratically as a function of a/λ, whereas the scattered wave pattern is independent of crack length for small cracks a << λ. This study of the forward scattering problem from a known crack size provides a useful guide for the inverse problem of hidden crack detection and sizing.


[Global gene response to GSM 1800 MHz radiofrequency electromagnetic field in MCF-7 cells].
To investigate whether GSM 1800 MHz radiofrequency electromagnetic field (RF EMF) can change the gene expression profile in MCF-7 cells and to screen RF EMF responsive genes. Subcultured MCF-7 cells were intermittently (5-minute fields on/10-minute fields off) exposed or sham-exposed to GSM 1800 MHz RF EMF, which was modulated by 217 Hz EMF, for 24 hours at an average specific absorption rate (SAR) of 2.0 W/kg or 3.5 W/kg. Immediately after RF EMF exposure or sham-exposure, total RNA was isolated from MCF-7 cells and then purified. Affymetrix Human Genome U133A Genechip was applied to examine the change of gene expression profile according to the manufacturer's instruction. Data was analyzed by Affymetrix Microarray Suite 5.0 (MAS 5.0) and Affymetrix Data Mining Tool 3.0 (DMT 3.0). Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to validate the differentially expressed genes identified by Genechip analysis. A small number of differential expression genes were found in each comparison after RF EMF exposure. Through reproducible and consistent analysis, no gene or five up-regulated genes were screened out after exposure to RF EMF at SAR of 2.0 W/kg or 3.5 W/kg, respectively. However, these five genes could not be further confirmed by RT-PCR. The present study did not provide clear evidence that RF EMF exposure might distinctly change the gene expression profile in MCF-7 cells under current experimental conditions, implying that the exposure might not affect the MCF-7 cell physiology, or this cell line might be less sensitive to the RF EMF exposure.


The role of cell adhesion molecules in visual circuit formation: from neurite outgrowth to maps and synaptic specificity.
The formation of visual circuitry is a multistep process that involves cell-cell interactions based on a range of molecular mechanisms. The correct implementation of individual events, including axon outgrowth and guidance, the formation of the topographic map, or the synaptic targeting of specific cellular subtypes, are prerequisites for a fully functional visual system that is able to appropriately process the information captured by the eyes. Cell adhesion molecules (CAMs) with their adhesive properties and their high functional diversity have been identified as key actors in several of these fundamental processes. Because of their growth-promoting properties, CAMs play an important role in neuritogenesis. Furthermore, they are necessary to control additional neurite development, regulating dendritic spacing and axon pathfinding. Finally, trans-synaptic interactions of CAMs ensure cell type-specific connectivity as a basis for the establishment of circuits processing distinct visual features. Recent discoveries implicating CAMs in novel mechanisms have led to a better general understanding of neural circuit formation, but also revealed an increasing complexity of their function. This review aims at describing the different levels of action for CAMs to shape neural connectivity, with a special focus on the visual system.


Acupuncture of different treatment frequencies in knee osteoarthritis: a pilot randomised controlled trial.
This 16-week randomised controlled trial (8-week treatment followed by 8-week follow-up) evaluated the symptomatic improvement in patients with knee osteoarthritis on 3 sessions per week of acupuncture (TSWA) compared to 1 session per week of acupuncture (OSWA). Sixty participants were randomised to either the TSWA or the OSWA group in a 1:1 ratio. The primary outcome was response rate, defined as the percentage of participants achieving ≥2 points decrease on the numerical rating scale (NRS) and ≥6 points decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at week 8 compared with baseline. Additional outcomes included response rates at weeks 4 and 16, NRS, WOMAC, Patient Global Assessment, 12-item Short Form Health Survey (SF-12), and treatment credibility and expectancy. No significant difference was seen in response rate between TSWA and OSWA groups at week 8 (64.7% vs 50.0%; difference, 14.7 percentage points [95% CI, -10.1 to 39.4 percentage points], P = 0.435). At weeks 4 and 16, the TSWA group had higher response rates than the OSWA group (week-4: difference, 44.7 percentage points [95% CI, 23.2-66.1 percentage points], P = 0.001; week-16: difference, 46.0 percentage points [95% CI, 24.4-67.6 percentage points], P < 0.001). Participants in the TSWA group experienced significantly greater improvements in NRS, WOMAC function, and Patient Global Assessment than those in the OSWA group. There were no significant between-group differences in WOMAC stiffness and SF-12. In summary, TSWA immediately improved knee pain and dysfunction compared with OSWA. In addition, the benefit of TSWA persists throughout follow-up.


Compositional and Functional Characteristics of Feta-Type Cheese Made from Micellar Casein Concentrate.
Micellar casein concentrate (MCC) is a high protein ingredient (obtained by microfiltration of skim milk) with an elevated level of casein as a percentage of total protein (TP) compared to skim milk. It can be used as an ingredient in cheese making. Feta-type cheese is a brined soft cheese with a salty taste and acid flavor. We theorize that Feta-type cheese can be produced from MCC instead of milk, which can improve the efficiency of manufacture and allow for the removal of whey proteins before manufacturing Feta-type cheese. The objectives of this study were to develop a process of producing Feta-type cheese from MCC and to determine the optimum protein content in MCC to make Feta-type cheese. MCC solutions with 3% (MCC-3), 6% (MCC-6), and 9% (MCC-9) protein were prepared and standardized by mixing water, MCC powder, milk permeate, and cream to produce a solution with 14.7% total solids (TS) and 3.3% fat. Thermophilic cultures were added at a rate of 0.4% to MCC solutions and incubated at 35 °C for 3 h to get a pH of 6.1. Subsequently, calcium chloride and rennet were added to set the curd in 20 min at 35 °C. The curd was then cut into cubes, drained for 20 h followed by brining in 23% sodium chloride solutions for 24 h. Compositional analysis of MCC solutions and cheese was carried out. The yield, color, textural, and rheological measurements of Feta-type cheese were evaluated. Feta-type cheese was also made from whole milk as a control. This experiment was repeated three times. The yield and adjusted yield of Feta-type cheese increased from 19.0 to 54.8 and 21.4 to 56.5, respectively, with increasing the protein content in MCC from 3% to 9%. However, increasing the protein content in MCC did not show significant differences in the hardness (9.2-9.7 kg) of Feta-type cheese. The color of Feta-type cheese was less white with increasing the protein content in MCC. While the yellowish and greenish colors were high in Feta-type cheese made from MCC with 3% and 6% protein, no visible differences were found in the overall cheese color. The rheological characteristics were improved in Feta-type cheese made from MCC with 6% protein. We conclude that MCC with different levels of protein can be utilized in the manufacture of Feta-type cheese.


Multivalent Targeting of the Asialoglycoprotein Receptor by Virus-Like Particles.
The asialoglycoprotein receptor (ASGPR) is expressed in high density on hepatocytes. Multivalent variants of galactosyl carbohydrates bind ASGPR with high affinity, enabling hepatic delivery of ligand-bound cargo. Virus-like particle (VLP) conjugates of a relatively high-affinity ligand were efficiently endocytosed by ASGPR-expressing cells in a manner strongly dependent on the nature and density of ligand display, with the best formulation using a nanomolar-, but not a picomolar-level, binder. Optimized particles were taken up by HepG2 cells with greater efficiency than competing small molecules or the natural multigalactosylated ligand, asialoorosomucoid. Upon systemic injection in mice, these VLPs were rapidly cleared to the liver and were found in association with sinusoidal endothelial cells, Kupffer cells, hepatocytes, dendritic cells, and other immune cells. Both ASGPR-targeted and nontargeted particles were distributed similarly to endothelial and Kupffer cells, but targeted particles were distributed to a greater number and fraction of hepatocytes. Thus, selective cellular trafficking in the liver is difficult to achieve: even with the most potent ASGPR targeting available, barrier cells take up much of the injected particles and hepatocytes are accessed only approximately twice as efficiently in the best case.


Phytogeographic patterns and cryptic diversity in an aposematic toad from NW Argentina.
The Yungas Redbelly Toad, Melanophryniscus rubriventris, is patchily distributed in Argentina, confined to the upland portion (1000-2000m above sea level) of the montane forests of northern and central regions of Salta, and in central-eastern and south-eastern Jujuy. This species is known for its striking aposematic color variation across its geographic distribution, and was once treated as a complex of three subspecies based on distinctive color patterns. Here we assess the geographical genetic variation within M. rubriventris and quantify divergence in color and pattern among individuals sampled from Northwestern Argentina. We compare multi-gene phylogeography of M. rubriventris to patterns of dorsal and ventral coloration to test whether evolutionary affinities predict variation in warning color. Our results reveal two well-supported species lineages: one confined to the extreme northern portion of our sampling area, and the other extending over most of the Argentine portion of the species' range, within which there are two populations. However, these well-supported evolutionary relationships do not mirror the marked variation in warning coloration. This discordance between DNA genealogy and warning color variation may reflect selection brought about by differences in local predation pressures, potentially coupled with effects of sexual selection and thermoregulation.


Prevalence of tet genes mediating tetracycline resistance in Escherichia coli clinical isolates in Osun State, Nigeria.
The occurrence of tetracycline resistance determinants in 203 Escherichia coli isolates recovered from clinical samples at three different hospitals in Nigeria between June 2009 and May 2010 was investigated. The isolates were subjected to standard procedures. Antibiotic susceptibility to a panel of eight antibiotics was also performed, and resistance genes were detected with the polymerase chain reaction (PCR) technique. One hundred and six E. coli isolates (52.2%) were obtained at LAUTECH Teaching Hospital Osogbo, 85 (41.9%) from OAUTHC Ile Ife and 12 (5.9%) from Osun State Hospital Asubiaro Osogbo. Result of the disk diffusion antibiotic susceptibility test showed 96.1% isolates to be resistant to ampicillin, 77.8% to tetracycline, 37.9% to cotrimoxazole, 38.4% to nalidixic acid, 20.7% to ofloxacin, 17.7% to ceftriaxone, 11.8% to gentamycin, and 2% to nitrofurantoin. One hundred and sixty two (79.9%) isolates had minimum inhibitory concentration (MIC) of tetracycline ≥ 128 μg/ml. The polymerase chain reaction (PCR) detected tetA gene in 89 (43.8%) isolates, tetB gene in 65 (32.0%), and both tetA and tetB genes in 9 (4.4%) isolates. The study demonstrated a relatively high level of gene mediated antibiotic resistance to tetracycline and other antibiotics in E. coli clinical isolates in Southwest region of Nigeria.


Prelabour rupture of the membranes at term--no advantage of delaying induction for 24 hours.
We performed a prospective randomized study to compare maternal and fetal outcomes in pregnancies with prelabour rupture of the membranes (PROM) at term with early induction of labour or expectant management, 126 women with singleton pregnancy, cephalic presentation and gestational duration > or = 37 weeks, were randomized either to immediate induction of labour with oxytocin (Group 1) (n=52), or conservative management (Group 2) (n=74). Women who constituted Group 2 were divided into 2 groups. The first group (Group 2A) (n=25) included women in whom spontaneous labour did not begin after a waiting period of 24 hours, in which case labour was induced with oxytocin i.e. expectant management. The second group consisted of women (Group 2B) (n=49) in whom labour began spontaneously within 24 hours. The base Caesarean section rate was significantly higher in Group 2 (28.4%) (p<0.05). The rates of Caesarean section in the Groups 1-2A-2B were 19.2%, 60%, and 12.2%, respectively for nulliparous and parous women together. The rate of fetal distress was significantly higher in Group 2 (p<0.05). For determining maternal outcomes, the other parameters such as clinical chorioamnionitis, fever before or during labour, receiving antibiotics before or during labour, postpartum fever, analgesia, anaesthesia did not differ in Groups 1 and 2. Women in Group 1 went into active labour sooner, had fewer digital vaginal examinations, had a shorter interval between membrane rupture and delivery, and spent less time in the hospital before delivery than those in Group 2 (p<0.05). Babies in Group 2 were more likely to receive antibiotics, and more likely to stay in an intensive care nursery for more than 24 hours, and more likely to receive ventilation after initial resuscitation than those babies in Group 1. For developing apnoea and hypotonia, there was no significant difference between Groups 1 and 2. However, for babies in Group 2A there was a significant difference. We conclude that immediate induction of labour with oxytocin does not increase the risk of Caesarean section, compared with a practice of expectant management. Women at term with prelabour rupture of the membranes should therefore be reassured that immediate induction with oxytocin currently appears to be the best policy with respect to maternal and neonatal morbidity.


Rapid and Recent Evolution of LTR Retrotransposons Drives Rice Genome Evolution During the Speciation of AA-Genome Oryza Species.
The dynamics of long terminal repeat (LTR) retrotransposons and their contribution to genome evolution during plant speciation have remained largely unanswered. Here, we perform a genome-wide comparison of all eight Oryza AA-genome species, and identify 3911 intact LTR retrotransposons classified into 790 families. The top 44 most abundant LTR retrotransposon families show patterns of rapid and distinct diversification since the species split over the last ∼4.8 MY (million years). Phylogenetic and read depth analyses of 11 representative retrotransposon families further provide a comprehensive evolutionary landscape of these changes. Compared with Ty1-copia, independent bursts of Ty3-gypsy retrotransposon expansions have occurred with the three largest showing signatures of lineage-specific evolution. The estimated insertion times of 2213 complete retrotransposons from the top 23 most abundant families reveal divergent life histories marked by speedy accumulation, decline, and extinction that differed radically between species. We hypothesize that this rapid evolution of LTR retrotransposons not only divergently shaped the architecture of rice genomes but also contributed to the process of speciation and diversification of rice.